Reviewed February 2012
What is the official name of the PEPD gene?
The official name of this gene is “peptidase D.”
PEPD is the gene's official symbol. The PEPD gene is also known by other names, listed below.
What is the normal function of the PEPD gene?
The PEPD gene provides instructions for making the enzyme prolidase, also called peptidase D. Prolidase helps divide certain dipeptides, which are molecules composed of two protein building blocks (amino acids). Specifically, prolidase divides dipeptides containing the amino acids proline or hydroxyproline. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs.
Prolidase is also involved in the final step of the breakdown of some proteins obtained though the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of collagens, a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix.
How are changes in the PEPD gene related to health conditions?
- prolidase deficiency - caused by mutations in the PEPD gene
At least 19 mutations in the PEPD gene have been identified in people with prolidase deficiency, a disorder with a wide variety of signs and symptoms including skin problems and intellectual disability. The PEPD gene mutations identified in people with prolidase deficiency result in the loss of prolidase enzyme activity.
It is not well understood how the absence of prolidase activity results in the various signs and symptoms of prolidase deficiency. Researchers have suggested that accumulation of dipeptides that have not been broken down may lead to cell death. When cells die, their contents are released into the surrounding tissue, which could cause inflammation and lead to the skin problems seen in prolidase deficiency. Impaired collagen breakdown during remodeling of the extracellular matrix may also contribute to the skin problems. The intellectual disability that occurs in prolidase deficiency might result from problems in processing neuropeptides, which are brain signaling proteins that are rich in proline. It is unclear how absence of prolidase activity results in the other features of prolidase deficiency.
Where is the PEPD gene located?
Cytogenetic Location: 19q13.11
Molecular Location on chromosome 19: base pairs 33,386,949 to 33,521,893
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/5184))
The PEPD gene is located on the long (q) arm of chromosome 19 at position 13.11.
More precisely, the PEPD gene is located from base pair 33,386,949 to base pair 33,521,893 on chromosome 19.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about PEPD?
You and your healthcare professional may find the following resources about PEPD helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK299584)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for PEPD (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5184%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28PEPD%5BTIAB%5D%29%20OR%20%28peptidase%20D%5BTIAB%5D%29%29%20OR%20%28%28PROLIDASE%5BTIAB%5D%29%20OR%20%28xaa-Pro%20dipeptidase%5BTIAB%5D%29%20OR%20%28imidodipeptidase%5BTIAB%5D%29%20OR%20%28X-Pro%20dipeptidase%5BTIAB%5D%29%20OR%20%28proline%20dipeptidase%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20NOT%20%28paroxysmal%20extreme%20pain%20disorder%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201440%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/613230)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_PEPD.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=8840)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5184)
What other names do people use for the PEPD gene or gene products?
- aminoacyl-L-proline hydrolase
- proline dipeptidase
- xaa-Pro dipeptidase
- X-Pro dipeptidase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding PEPD?
extracellular matrix ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Falik-Zaccai TC, Khayat M, Luder A, Frenkel P, Magen D, Brik R, Gershoni-Baruch R, Mandel H. A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability. Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):46-56. doi: 10.1002/ajmg.b.30945. (http://www.ncbi.nlm.nih.gov/pubmed/19308961?dopt=Abstract)
- Forlino A, Lupi A, Vaghi P, Icaro Cornaglia A, Calligaro A, Campari E, Cetta G. Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts. Hum Genet. 2002 Oct;111(4-5):314-22. Epub 2002 Aug 14. (http://www.ncbi.nlm.nih.gov/pubmed/12384772?dopt=Abstract)
- Lupi A, De Riso A, Torre SD, Rossi A, Campari E, Vilarinho L, Cetta G, Forlino A. Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure-function relationship. J Hum Genet. 2004;49(9):500-6. Epub 2004 Aug 11. (http://www.ncbi.nlm.nih.gov/pubmed/15309682?dopt=Abstract)
- Lupi A, Rossi A, Campari E, Pecora F, Lund AM, Elcioglu NH, Gultepe M, Di Rocco M, Cetta G, Forlino A. Molecular characterisation of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family. J Med Genet. 2006 Dec;43(12):e58. (http://www.ncbi.nlm.nih.gov/pubmed/17142620?dopt=Abstract)
- Lupi A, Tenni R, Rossi A, Cetta G, Forlino A. Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. Amino Acids. 2008 Nov;35(4):739-52. doi: 10.1007/s00726-008-0055-4. Epub 2008 Mar 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18340504?dopt=Abstract)
- Mitsubuchi H, Nakamura K, Matsumoto S, Endo F. Inborn errors of proline metabolism. J Nutr. 2008 Oct;138(10):2016S-2020S. (http://www.ncbi.nlm.nih.gov/pubmed/18806117?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5184)
- OMIM: PEPTIDASE D (http://omim.org/entry/613230)
- Surazynski A, Donald SP, Cooper SK, Whiteside MA, Salnikow K, Liu Y, Phang JM. Extracellular matrix and HIF-1 signaling: the role of prolidase. Int J Cancer. 2008 Mar 15;122(6):1435-40. (http://www.ncbi.nlm.nih.gov/pubmed/17999410?dopt=Abstract)
- Wang H, Kurien BT, Lundgren D, Patel NC, Kaufman KM, Miller DL, Porter AC, D'Souza A, Nye L, Tumbush J, Hupertz V, Kerr DS, Kurono S, Matsumoto H, Scofield RH. A nonsense mutation of PEPD in four Amish children with prolidase deficiency. Am J Med Genet A. 2006 Mar 15;140(6):580-5. (http://www.ncbi.nlm.nih.gov/pubmed/16470701?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.